FDA Approves Durvalumab Plus Standard of Care Chemo for Extensive-Stage SCLC

The FDA approved durvalumab (Imfinzi) as a first-line treatment for adult patients with extensive-stage small cell lung cancer (ES-SCLC) in combination with standard-of-care (SOC) chemotherapies, etoposide plus either carboplatin or cisplatin (platinum-etoposide), according to AstraZeneca, the agent’s developer.

The approval was based on positive results from the phase III CASPIAN trial, which found that durvalumab in combination SOC platinum-etoposide demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), versus SOC alone. 

“The US approval of Imfinzi brings a new medicine to extensive-stage small cell lung cancer patients in urgent need of new options,” Dave Fredrickson, executive vice president of the Oncology Business Unit, said in a press release. “Imfinzi is the only immunotherapy to show both a significant survival benefit and improved response rate in combination with chemotherapy for these patients, an important step forward in treating this devastating disease.”

In the phase III CASPIAN trial, published in The Lancet, researchers had 2 primary endpoints which compared experimental arms to SOC. Researchers conducted the trial in more than 200 centers across 23 countries, including the US, Europe, South America, Asia, and the Middle East. The trial used a fixed dose of 1,500 mg durvalumab administered every 3 weeks for 4 cycles while in combination with chemotherapy, and then every 4 weeks until disease progression. 

In the durvalumab plus SOC arm, the risk of death was reduced by 27% (equal to hazard ratio of 0.73; 95% CI, 0.59-0.91; P = 0.0047), with median OS of 13.0 months versus 10.3 months for SOC alone. Moreover, the results also showed an increase confirmed objective response rate in the durvalumab plus SOC arm (68% vs 58%). The safety and tolerability for durvalumab plus SOC was found to be consistent with the known safety profiles of these medicines. 

The second experimental arm testing tremelimumab added to durvalumab and SOC was only recently completed, however it did not meet its primary endpoint. Details for this arm will be presented at an upcoming medical meeting. 

“Patients with extensive-stage small cell lung cancer continue to face a poor prognosis, and finding new medicines to improve outcomes in this setting has been a formidable challenge,” Jonathan Goldman, MD, associate professor of Hematology & Oncology at the UCLA Medical Center in Santa Monica, California, said in a press release. “The CASPIAN trial enables clinicians to choose durvalumab in combination with etoposide and either carboplatin or cisplatin, making this an important new first-line treatment option for patients that is both effective and well-tolerated.” 

As part of a broad development program, researchers are also testing durvalumab following concurrent chemoradiation therapy in patients with limited-stage SCLC in the phase III ADRIATIC trial. Data from this study is anticipated in 2021. 

Durvalumab received its first approval based on the phase III CASPIAN trial in Singapore for patients with ES-SCLC in February 2020. Additionally, durvalumab in combination with etoposide and either carboplatin or cisplatin is currently under regulatory review for the treatment of ES-SCLC in the first-line setting based on the phase III CASPIAN trial in the EU and Japan. 

Further, durvalumab is approved in the curative-intent setting of resectable, stage III non-small cell lung cancer after chemoradiation therapy in the US, Japan, China, across the EU, and in several other countries based on the phase III PACIFIC trial. The PD-1/PD-L1 immunotherapy is also approved for the first-line treatment of ES-SCLC in combination with SoC chemotherapy in the US and Singapore and for previously treated patients with advanced bladder cancer in the US and a small number of other countries. 

Reference:

Imfinzi approved in the US for extensive-stage small cell lung cancer [news release]. Published March 30, 2020. astrazeneca.com/content/astraz/media-centre/press-releases/2020/imfinzi-approved-in-the-us-for-extensive-stage-small-cell-lung-cancer.html. Accessed March 30, 2020.